Shaping the Future of Obesity Treatment: In Silico Multi-Modeling of IP6K1 Inhibitors for Obesity and Metabolic Dysfunction.

Recent research has uncovered a promising approach to addressing the growing global health concern of obesity and related disorders. The inhibition of inositol hexakisphosphate kinase 1 (IP6K1) has emerged as a potential therapeutic strategy. This study employs multiple ligand-based in silico modeling techniques to investigate the structural requirements for benzisoxazole derivatives as IP6K1 inhibitors. Firstly, we developed linear 2D Quantitative Structure-Activity Relationship (2D-QSAR) models to ensure both their mechanistic interpretability and predictive accuracy. Then, ligand-based pharmacophore modeling was performed to identify the essential features responsible for the compounds' high activity. To gain insights into the 3D requirements for enhanced potency against the IP6K1 enzyme, we employed multiple alignment techniques to set up 3D-QSAR models. Given the absence of an available X-ray crystal structure for IP6K1, a reliable homology model for the enzyme was developed and structurally validated in order to perform structure-based analyses on the selected dataset compounds. Finally, molecular dynamic simulations, using the docked poses of these compounds, provided further insights. Our findings consistently supported the mechanistic interpretations derived from both ligand-based and structure-based analyses. This study offers valuable guidance on the design of novel IP6K1 inhibitors. Importantly, our work exclusively relies on non-commercial software packages, ensuring accessibility for reproducing the reported models.

Mapping of tide-dominated Hooghly estuary water quality parameters using Sentinel-3 OLCI time-series data.

The study explores the spatio-temporal variation of water quality parameters in the Hooghly estuary, which is considered an ecologically-stressed shallow estuary and a major distributary for the Ganges River. The estimated parameters are chlorophyll-a, total suspended matter (TSM), and chromophoric dissolved organic matter (CDOM). The Sentinel-3 OLCI remote sensing imageries were analyzed for the duration of October 2018 to February 2019. We observed that the water quality of the Hooghly estuaries is comparatively low-oxygenated, mesotrophic, and phosphate-limited. Ongoing channel dredging for maintaining shipping channel depth keeps the TSM in the estuary at an elevated level, with the highest amount of TSM observed during March of 2019 (41.59g m-3) at station A, upstream point. Since the pre-monsoon season, TSM data shows a decreasing trend towards the mouth of the estuary. Chl-a concentration is higher during pre-monsoon than monsoon and post-monsoon periods, with the highest value observed in April at 1.09 mg m-3 in station D during the pre-monsoon period. The CDOM concentration was high in the middle section (January-February) and gradually decreased towards the estuary's head and mouth. The highest CDOM was found in February at locations C and D during the pre-monsoon period. Every station shows a significant correlation among CDOM, TSM, and Chl-a measured parameters. Based on our satellite data analysis, it is recommended that SNAP C2RCC be regionally used for TSM, Chl-a, and CDOM for water quality product retrieval and in various algorithms for the Hooghly estuary monitoring.

Estimation of agricultural burned affected area using NDVI and dNBR satellite-based empirical models.

One of the major crucial issues that need worldwide attention is open stubble burning, which imposes a variety of adverse impacts on nature and human society, destroying the world's biodiversity. Many earth observation satellites render information to monitor and assess agricultural burning activities. In this study, different remotely sensed data (Sentinel-2A, VIIRS) has been employed to estimate the quantitative measurements of agricultural burned areas of the Purba Bardhaman district from October-December 2018. The multi-temporal image differencing techniques and indices (NDVI, NBR, and dNBR) and VIIRS active fires data (VNP14IMGT) have been utilized to spot agricultural burned areas. In the case of the NDVI technique, a prominent area, 184.82 km2 of agricultural burned area (7.85% of the total agriculture), was observed. The highest (23.04 km2) burned area was observed in the Bhatar block, located in the middle part of the district, and the lowest (0.11 km2) burned area was observed in the Purbasthali-II block, which is located in the eastern part of the district. On the other hand, the dNBR technique revealed that the agricultural burned areas enwrap 8.18% of the total agricultural area, which is 192.45 km2. As per the earlier NDVI technique, the highest agricultural burned areas (24.82 km2) were observed in the Bhatar block, and the lowest (0.13 km2) burn area occurred in the Purbashthali-II block. In both cases, it is observed that agricultural residue burning is high in the western part of the Satgachia block and the adjacent areas of the Bhatar block, which is in the middle part of Purba Bardhaman. The agricultural burned area was extracted using different spectral separability analyses, and the performance of dNBR was the most effective in spectral discrimination of burned and unburned surfaces. This study manifested that agricultural residue burning started in the central part of Purba Bardhaman. Later it spread all over the district due to the trend of early harvesting rice crops in this region. The performance of different indices for mapping the burned areas was evaluated and compared, revealing a strong correlation (R2) = 0.98. To estimate the campaign's effectiveness against the dangerous practice and plan the control of the menace, regular monitoring of crop stubble burning using satellite data is required.

Comparative analysis of statistical methods for landslide susceptibility mapping in the Bostanlik District, Uzbekistan.

The Bostanlik district, Uzbekistan, is characterized by mountainous terrain susceptible to landslides. The present study aims at creating a statistically derived landslide susceptibility map - the first of its type for Uzbekistan - for part of the area in order to inform risk management. Statistical index (SI), frequency ratio (FR) and certainty factor (CF) are employed and compared for this purpose. Ten predictor layers are used for the analysis, including geology, soil, land use and land cover, slope, aspect, elevation, distance to lineaments, distance to faults, distance to roads, and distance to streams. 170 landslide polygons are mapped based on GeoEye-1 and Google Earth imagery. 119 (70%) out of them are randomly selected and used for the training of the methods, whereas 51 (30%) are retained for the evaluation of the results. The three landslide susceptibility maps are split into five classes, i.e. very low, low, moderate, high, and very high. The evaluation of the results obtained builds on the area under the success rate and prediction rate curves (AUC). The training accuracies are 82.1%, 74.3% and 74%, while the prediction accuracies are 80%, 70% and 71%, for the SI, FR and CF methods, respectively. The spatial relationships between the landslides and the predictor layers confirmed the results of previous studies conducted in other areas, whereas model performance was slightly higher than in some earlier studies - possibly a benefit of the polygon-based landslide inventory.